Wednesday, January 26, 2011

A discussion of a report on the multimillion dollar costs of 510(k)s is showing up on several websites/blogs. As it stands it can be highly misleading. While some companies may in fact have spent that total dollar amount cited, $24 Million USD, to get a product to the point where it has received a 510(k)clearance, to say 77% is tied to regulatory costs is very misleading. To arrive at those figures, those costs have to include features, documentation, engineering, testing, validation, personnel salaries, et al, activites that may be required under the cGMPs but are really related to product / use safety and quality.
Does any one seriously argue that many bench / functional testing, biocompatibility testing, sterilization, documentation systems, validations (including software), the other basics (including principles of Shewhart, Deming,Juran, et al) required under the cGMP quality management systems and its infrastructure, and yes, some clinical trials, should not be required? I've worked for years (28+) on medical device projects (the last 16 as a consultant), 510(k)s, validations, and unless the above are added to the equation, the figures quoted and attributable to FDA regulatory / clearance costs are completey unrealistic.
I for one would not want a device used on me or my loved ones that had not proved its safety and quality by such testing, and manufactured, labeled, tested / validated, packaged, and sterilized under documented / validated systems. True, some points raised about inefficiences, uncertainties, delays, personnel qualifications, unnecessary or redundant activities,et al, are valid (but nowhere near the dollars implied), and not just on the FDA side, but also on the manufacturer's side, including their submissions. Some companies even report other companies' violations to the FDA to "level the playing field".
The majority of the Stanford Report itself raises legitimate questions, and certainly the conclusions of EU / other 'reputable', regulatory bodies should be strongly considered by the U.S. FDA, 'tho there are dangers (remember the drug thalidomide). However, a key point on costs, page 28, leaves the reader to guess what really contributes to the costs per month due to delays (idle personnel, borrowing costs / interest on loans, lost opportunity costs, or ...). In fact, the last sentence on that page opens up major questions ("liklihood", "self-selected" ... ) that beg answers to really justify the headlines given this study.
Many requirements work to a company's advantage, e.g., design control and fast cycle development, documentation and liability / IP / minimal "reinventing the wheel", reduced recalls (some recent events w/ treated wood pallets and odor- contaminated product for two major pharma companies come to mind). Of course such benefits are only realized IF (a big 'if') companies use them for business reasons, not just to satisfy regulatory / bureacratic procedures.

U.S. FDA'S 510(K) WORKING GROUP FINDINGS, AUGUST 2010As I am actively involved in compiling and submitting 510(k)s for clients, I find the August 2010 Working Group findings on 510(k)s to be a useful tool. Current indications are that these findings may not be immediately implemented. However, they indicate some of the concerns re: the 510(k) process, and it may be wise to address those that affect product safety or indicate a company's efforts to increase device safety. My 510(k) submissions address many of the recommendations as if they were already implemented, especially in showing safety. I do this primarily in two ways: 1) by including an ISO 14971-based hazard analysis / risk management file that includes an FTA and FMECA; and 2) by also performing an analysis of the FDA's MAUDE database for that family of product, and include that analysis in the submission. A complete product description seems like a "no brainer", but it's best not to assume anything and address even the most basic elements in a device description and in the SE / predicate(s) comparison matrix. It is also useful to incorporate principles from all regulated industries, not just devices, to address stated and anticipated FDA (and patient / clinician / user) concerns (e.g., the ICH Q-series principles and HACCP techniques). -- J. E. Lincoln and Associates LLC Medical Device Consulting: http://www.jelincoln.com/

Many ask what's involved in obtaining 510(k) clearance for FDA-defined Class II medical devices for sale in the U.S. The following is my typical response:

The product would essentially have to be almost the same, if not the same (substantially equivalent) as a previously cleared product (the predicate), with the same safety and efficacy issues. Any variation would have to be extensivelly tested by a testing company or lab. And to prove being identical, similar testing would also be required. Several international labs can provide a list of tests and their costs. These tests would be included in the 510(K) submission together w/ labeling, packaging, etc.

The FDA charges a fee to review a 510(k) with no guarantees, ~$4100.00+ USD (payable at time of submission; which can be reduced if the company can show it meets their definition of a small business a 60 day review). The parent company would have to be registered with the FDA (another fee of over $3000.00) and have a compliant cGMP system in place, and its suppliers would need the same. Consultants such as myself provide assistance in those areas as well (or the company, or another party could do) at additional costs.

Charges run the gamut, from lows in the $4-5000's to $10,000 or more depending upon consultant and project complexity, with costs going higher if an IDE (Investigation Device Exemption) / clinicals are involved. IDE's can cost as much as a 510(k) since they address much of the same requirements. Some consultants, such as myself, make charges payable in 1/3s, with the first third up front, prior to start on the 510(k). Product risk analysis per ISO 14971 is usually several thousand dollars extra, unless a company already has their own. The company would be required to pay all the test fees and FDA fees, such as those mentioned above. And there would be no guarantees (the FDA is currently evaluating and tightening their 510(k) requirements).

And there are no guarantees. If your product is basically identical to the pedicate(s) then clearance is likely. Any differences raise the chance of the submission being found NSE (not substantially equivalent). If such happens, there are several options:
1. Immediately refile a "de novo" application (if product is low risk);
2. Go back to the "drawing board" to address major issues, and refile another 510(k), with new fees;
3. File a PMA which is more expensive and can take several years.

Friday, January 21, 2011

Welcome to my new blog -- CGMP Issues. CGMP stands for current Good Manufacturing Practices, and specifically refers to the U.S. Code of Federal Regulations, Parts 111 (dietary supplements), 210/211 (pharma), and 820 (medical devices). We will discuss points of interest to the U.S. FDA-regulated industries, focusing on medical devices, but with some elements of pharmaceuticals, combination products, dietary supplements and related. Please indicate your company's areas of concern and we will try to address them or direct you to the appropriate resource. See my website: http://www.jelincoln.com/